In the last couple of decades, the use of biomarkers has become increasingly intrinsic to the practice of medicine and clinical decision-making Clinicians and researchers have rapidly been identifying biomarkers for clinical conditions ranging from heart disease and cancer, to Alzheimer's and dementia, to drug overdose and epilepsy. The number of published articles on biomarkers has increased substantially from under 200 in the early 1990s to well over 24,000 in the year 2011. This explosion in publication has meant that the last two decades have seen over 157,000 scientific publications.
This increasing interest in biomarkers is the result of their potential in heralding the much spoken of revolution in personalized medicine. However, biomarker testing has failed to be implemented in the clinical environment, and many different barriers prevent the complete utilization of biomarker testing.
First, only about 1 protein biomarker per year is approved by the Food and Drug Administration (FDA) for all diagnostic indications. Without regulatory approval, biomarker discoveries remain academic curiosities that simply do not impact patient care. The tools needed to facilitate the move of discoveries from validation into clinical implementation is lacking.
Second, the absence of a standard platform and pathway for approval has resulted in a ‘biomarker bottleneck’ that has prevented the highly anticipated revolution in personalized medicine from occurring.
Additionally, the lack of point-of-care analysis tools has limited biomarker based clinical decisions to far-off labs requiring delays between testing and treatment planning.
To address some of these issues, the McDevitt Research Group of Rice University (formerly of the University of Texas at Austin) has been developing and perfecting a novel bead based assay system called Programmable Bio-Nano-Chip and described in e.g. WO2012154306, WO2012065117, and WO2012065025.
Programmable Bio-Nano-Chip or “pBNC” utilizes microfluidics and advanced biochemistry to provide a rapid and easy-to-use method for obtaining quantitative biomarker assessments with potential use at the point-of-care, measuring various analyte species such as cells, proteins, small molecules, and DNA. “Programmable” describes the ability to chemically encode the pBNC to respond to different biomarkers. “Bio” refers to the capacity to isolate and quantify specific biomarkers from blood or saliva samples. “Nano” describes the scale of biomarker capture via nano-nets. “Chip” refers to the potential for mass production of pBNC components. By utilizing the principles of microfluidics and a lab-on-a-chip approach, the pBNC assays provide a way for monitoring multiple biomarkers simultaneously, require drastically reduced volumes of chemical reagents, and can provide a biomarker diagnosis in minutes as compared to the week long-wait times of market available lab-based tests.
The bio-specimens and reagents are guided and delivered via a set of microfluidic pathways, etched into the lab card, onto the beads where the reaction takes place. Once the blood sample and reagents have arrived at the microbeads, a set of biochemical reactions take place which trigger the beads to fluoresce proportionally to the concentration of the biomarker of interest. Digital images of these beads can then be obtained using a simple laboratory-based fluorescence microscope, portable analyzer, or other optical devices and then processed by data analysis software to convert the fluorescent intensity into a biomarker concentration.
Despite significant advances in development of miniaturized sensing and analytical devices for use in clinical and biomedical applications, the ability to interface individual components to achieve high level of integration continues to pose a challenge for the lab-on-chip (“LOC”) community. The heavy reliance on bulky pieces of equipment like syringe pumps, fluorescence microscopes, and infrastructure for analyzing the LOC devices can at times make such prototypes seem like chips-in-a-lab rather than true lab-on-chip devices.
Thus, with point-of-care applications, there is a need for a smaller system for performing biomarker analysis. Ideally, this system would act as a mobile analysis hub, capable of analyzing various biomarker concentrations.